Hispolon, a phenolic compound isolated from Phellinus igniarius, induces apoptosis and anti-tumor effects in cancers. However, the molecular mechanism involved in hispolon-mediated tumor-suppressing activities observed in cervical cancer is poorly characterized. Here, we demonstrated that treatment with hispolon inhibited cell metastasis in two cervical cancer cell lines. In addition, the downregulation of the lysosomal protease Cathepsin S (CTSS) was critical for hispolon-mediated suppression of tumor cell metastasis in both in vitro and in vivo models. Moreover, hispolon induced autophagy, which increased LC3 conversion and acidic vesicular organelle formation. Mechanistically, hispolon inhibited the cell motility of cervical cells through the extracellular signal-regulated kinase (ERK) pathway, and blocking of the ERK pathway reversed autophagy-mediated cell motility and CTSS inhibition. Our results indicate that autophagy is essential for decreasing CTSS activity to inhibit tumor metastasis by hispolon treatment in cervical cancer; this finding provides a new perspective on molecular regulation.

Carbonic anhydrase IX (CAIX) is a hypoxia-induced protein that is highly expressed in numerous human cancers. However, the molecular mechanisms involved in CAIX and human cervical cancer metastasis remain poorly understood. In this study, CAIX overexpression in SiHa cells increased cell migration and epithelial-to-mesenchymal transition (EMT). Silencing CAIX in the Caski cell line decreased the motility of cells and EMT. Furthermore, the RNA-sequencing analysis identified a target gene, bifunctional 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB4), which is influenced by CAIX overexpression and knockdown. A positive correlation was found between CAIX expression and PFKFB4 levels in the cervical cancer of the TCGA database. Mechanistically, CAIX overexpression activated the phosphorylation of extracellular signal-regulated kinases (ERKs) to induce EMT and promote cell migration. In clinical results, human cervical cancer patients with CAIXhigh/PFKFB4high expression in the late stage had higher rates of lymph node metastasis and the shortest survival time. Our study found that CAIX overexpression increases PFKFB4 expression and EMT, promoting cervical cancer cell migration. CAIX could contribute to cervical cancer cell metastasis and its inhibition could be a cervical cancer treatment strategy.

Fine sediments, which account for the majority of total fluvial sediment flux, have been suggested to degrade coral reefs on a global scale. Furthermore, sediment impacts can be exacerbated by extreme rainfall events associated with global climate change and anthropogenic nutrient enrichment. We report the findings from a series of mesocosm experiments exploring the effects of short-term sedimentation and nutrient enrichment on the interactions between the hard coral Acropora muricata, the sea anemone Mesactinia ganesis, and the green macroalga Codium edule. Mesocosms were manipulated to simulate either unimpacted reefs or reefs exposed to elevated levels of fine sediments for 10 or 14 days to simulate the effects of heavy rainfall. The first and second experiments were aimed to examine the effects of inorganic and organic sediments, respectively. The third experiment was designed to examine the interactive effects of nutrient enrichment and elevated sediment loads. Neither inorganic nor organic sediment loadings significantly affected the physiological performance of the coral, but, importantly, did reduce its ability to compete with other organisms. Photosynthetic efficiencies of both the green macroalga and the sea anemone increased in response to both sediment loadings when they were simultaneously exposed to nutrient enrichment. While organic sediment loading increased the nitrogen content of the green macroalga in the first experiment, inorganic sediment loading increased its phosphorus content in the second experiment. The coral mortality due to sea anemones attack was significantly greater upon exposure to enriched levels of organic sediments and nutrients. Our findings suggest that the combined effects of short-term sedimentation and nutrient enrichment could cause replacement of corals by sea anemones on certain coral reefs.

Diphenyl difluoroketone (EF-24), a synthetic curcumin analog, has enhanced bioavailability over curcumin. EF-24 acts more powerful bioactivity for anti-inflammatory and anti-cancer activity. However, the effects and mechanism of EF-24 on cervical cancer has not been fully investigated. Herein, this study evaluated the effects of EF-24 on TPA-induced cellular migration of cervical cancer. The results showed that EF-24 substantially reduced the cellular migration and cellular invasion of the HeLa and SiHa cells. Moreover, gelatin zymography, western blotting analyses and real-time PCR revealed that EF-24 suppressed Matrix metalloproteinase-9 (MMP-9) activity, protein expression and mRNA levels. Mechanistically, EF-24 inhibited the phosphorylation of the p38 signaling pathway. In conclusion, EF-24 inhibited TPA-induced cellular migration and cellular invasion of cervical cancer cell lines through modulating MMP-9 expression via downregulating signaling p38 pathway and EF-24 may have potential to serve as a chemopreventive agent of cervical cancer.